Cannabinoids are a group of chemicals from Cannabis sativa or Cannabis indica plant that are known to activate cannabinoid receptors (CB1 and CB2) in cells. These chemicals are also produced endogenously in humans and other animals and are termed endocanabinoids. Synthetic cannabinoids are manmade chemicals with the same structure as plant cannabinoids or endocanabinoids. Cannabinoids are cyclic molecules exhibiting particular properties such as the ability to easily cross the blood-brain barrier, weak toxicity and few side effects.
Δ9-Tetrahydrocannabinol (THC), represented by Formula (a), is the main psychoactive cannabinoid produced by the Cannabis Species which is well characterized for its biological activity and potential therapeutic application in a broad spectrum of diseases.
Cannabidol (CBD), represented by Formula (b), is another major constituent of Cannabinoids. CBD acts as an inverse agonist of the CB1 and CB2 cannabinoid receptors. CBD is a phytocannabinoid which unlike THC does not produce the psychoactive effects in humans. CBD is reported to exert analgesic, antioxidant, anti-inflammatory, and immunomodulatory effects.
The use of Cannabis as a medicine has been known since antiquity, but until recent times administration of complex Cannabis preparations (such as containing both THC and CBD) could only be achieved by delivery in ethanol or edible oils which were swallowed, or by the patient inhaling the vapors of Cannabis by smoking the dried plant material. Further, the psychoactive activity of THC has led to reluctance of public acceptance of medicines including this compound.

THC may exist in a decarboxylated form or in a non-decarboxylated, Tetrahydrocannbinolic acid (THCA) form (FIG. 2). The decarboxylated form after consumption is extremely psychoactive whereas the non-decarboxylated form after consumption is drastically-less psychoactive. Fully-decarboxylated THC, the main psychotropic component of Cannabis sativa, is much more psychoactive when consumed in its fully-decarboxylated form as opposed to when it is consumed in its non-decarboxylated form. After consumption, fully-decarboxylated THC formulated in conjunction with CBD exhibits a plethora of complex actions including psychoactivity, anti-convulsivity, sedative, hypnotic, anti-nausea, and anti-hyperalgesic properties (Mechoulam et al., 2002; Costa et al., 2007). THC in conjunction with CBD can also reduce some types of inflammation, the complex biological response organs, tissues and cells have to harmful stimuli such as pathogens, damage, or irritants. The use of the formulations based on fully-decarboxylated THC with CBD is of significant interest because these formulations function as unique high-potency cannabinoid receptor agonists for both cannabinoid CB1 and CB2 receptors (Pertwee et al., 2007).
The Cannabinoids and the THC-CBD combinations have been known in the art for treating or preventing a number of diseases or disorders. For example, U.S. Pat. No. 6,630,507 discloses Cannabinoids for use as anti-oxidants and neuro-protectants; U.S. Pat. No. 7,105,685 discloses Cannabinoids for the treatment of diseases associated with immune dysfunction, particularly HIV disease and neoplastic disorders; U.S. Pat. No. 7,109,245 discloses Cannabinoids useful as vasoconstrictors; US Patent Publication US20110257256 discloses THC-CBD composition for use in treating or preventing Cognitive Impairment and Dementia; PCT Publication WO/2009/147439 discloses use of a combination THC and CBD in the manufacture of a medicament for use in the treatment of cancer, in particular the glioma tumour; PCT Publication WO/2007/148094 discloses use of THC-CBD composition for the treatment of neuropathic pain; and US Patent Publication US20100286098 discloses a method of treating tissue injury in a patient with colitis administering the THC-CBD combination.
Surprisingly, the Applicant of the present invention has found that a novel composition comprising fully decarboxylated THC and CBD along with one or more small molecule(s) such as citric acid, ascorbic acid, sugar(s), greatly enhances the therapeutic potency of THC while exploiting a concurrent enhancement in its psychoactivity which is fully negated relative to perception in vivo by counter balance by inclusion of CBD.
Till date, no one has disclosed a finding of a relationship regarding psychoactivity in fully-decarboxylated THC and the compositions of THC, CBD, and one or more small molecules as described hereinafter, which has greatly enhanced pharmacological action and exhibited an increased but negated psychoactivity.
There is thus an unmet need for exploiting enhanced therapeutic potential and psychoactivity of THC for the treatment or prevention of one or more disease(s) or condition(s) modulated by the activation of the Cannabinoid CB1 and/or CB2 receptors. The present invention satisfies these needs, as well as others.